Trace Metal Tests

Definition

Trace metals are a group of metals that include both heavy and transitional elements present in sub-milligram quantities in the blood. There are two groups, the micronutrients that are essential for health and those that have no known biological function. The essential micronutrients that may be measured include arsenic, chromium, cobalt, copper, iron, manganese, nickel, selenium, and zinc. Rarely, molybdenum, tin, and vanadium may also be measured. The nonessential metals that may be measured are lead, mercury, aluminum, thallium, and cadmium.

Purpose

All trace metals have the potential to be toxic when present in excessive concentrations. Trace metal tests are required when the patient has symptoms of toxicity or when the patient is in a high risk category for environmental exposure to a toxic metal. Excessive amounts of a trace metal can cause specific diseases or abnormalities that will require medical intervention and removal of the metal by chelation therapy. Deficiencies of micronutrients including iron, zinc, copper, and selenium are common and can lead to significant medical problems. Tests for these metals are sometimes needed in order to diagnose essential trace metal deficiency and its cause.

Precautions

A blood sample or urine sample is required for trace metal testing. When performing venipuncture, the nurse or phletobomist collecting the sample should observe universal precautions for prevention of transmission of bloodborne pathogens. Trace metal contamination is a potentially serious problem with samples for trace metal analysis. Metals are present in the materials used to manufacture rubber stoppers and lubricants used in blood collection tubes. Therefore, special tubes with lubricant-free stoppers are required. Samples for lead analysis require whole blood because the lead is primarily within the red blood cells. Special tubes containing heparin or EDTA (ethylenediaminetetraacetic acid) are used for this purpose. These have a tan colored stopper and are certified to be lead free. Other trace metals are usually measured in serum or urine. If serum is used, the blood must be collected in a tube having a navy blue stopper. The only exception is iron, which is present in sufficient concentration in serum or plasma to allow use of regular blood collection tubes. In addition, when performing analysis of any trace metal, the water used must by Type I purity, and the reagents must meet or exceed American Chemical Society (ACS) purity standards.

Description

Measurement techniques

With the exception of iron, the method of choice for routine trace metal measurement is atomic absorption spectrophotometry with a graphite furnace atomizer. The instrument should be capable of background absorbance correction. Iron is the trace metal in highest concentration in plasma and can be measured by colorimetric methods. Other suitable methods for trace metal analysis include inductively coupled plasma mass spectroscopy and emission spectroscopy.

The following list represents both essential and nonessential trace metals that are measured in the medical laboratory. The most commonly measured metal and the only one routinely measured as part of a comprehensive metabolic profile is iron. The principal reason for measuring iron is to detect iron deficiency states that lead to anemia, or excessive iron ingestion that leads to tissue damage caused by excessive deposition of iron in tissues such as the liver. The most commonly measured nonessential metal is lead. There are many environmental sources of lead, but it is especially prevalent in paint chips, lead pipes, car exhaust, and cigarette smoke. Young children are at greatly increased risk because they absorb up to five times more lead from the intestinal tract than adults. Since lead exposure during childhood can result in diminished intellectual ability, many medical centers have established lead screening programs in high pre-valence areas.

A brief description of the major effects of the trace metals listed above follows:

• Aluminum (Al): Toxic levels are found in patients with chronic kidney failure who have received hemodialysis over long periods of time; the dialysis solutions contain aluminum. Also at risk are diabetic patients (aluminum is present in medications) and those who ingest large quantities of antacids containing aluminum. Excess aluminum is deposited in the brain and in bone. Aluminum is a potent inhibitor of parathyroid hormone and induces osteomalacia. Central nervous system toxicities include convulsions, behavior, and speech disturbances.
• Arsenic (As): The organic form of arsenic is nontoxic but the ionic form is toxic. Arsenic is found in some herbicides, pesticides, insecticides, and seafood. Excessive amounts usually result from ingestion of poisons containing arsenic. Symptoms vary depending upon whether exposure is acute or chronic. Acute toxicity causes nausea, vomiting, abdominal pain, diarrhea, cardiac arrhythmia, and kidney damage; and very high doses can induce coma. Chronic exposure causes dermatitis, abnormal nail growth pattern, headache, drowsiness, confusion, and bone marrow failure.
• Cadmium (Cd): Cadmium is used to manufacture batteries and is used extensively in automotive spray painting. It is also prevalent in industrial pollution and in cigarette smoke. Breathing excessive amounts can cause lung damage (emphysema ). Ingestion or inhalation causes dizziness, headache, and intestinal irritation. Chronic exposure causes damage to the renal tubules known as heavy metal nephrosis.
• Chromium (Cr): Chromium is used to manufacture stainless steel, tan leather, and dye fabrics. Breathing excessive amounts can cause lung cancer. Chromium is also a skin irritant and excessive exposure to skin leads to ulceration.
• Cobalt (Co): Cobalt is used in various industrial processes, and inhalation of cobalt in dust can cause asthma. Symptoms include goiter, nerve damage, excessive blood cell production, and cardiomyopathy.
• Copper (Cu): Copper is the third most abundant trace metal and deficiency is more common than toxicity. The most common cause of copper deficiency is total parenteral nutrition. This leads to anemia, bone loss, hyperlipidemia, impaired immune function, and glucose intolerance. Copper toxicity is associated with a genetic deficiency of ceruloplasmin, Wilson's disease. This results in copper accumulation in the liver, eyes, kidney, and brain which is fatal without chelation therapy.
• Iron (Fe): Iron is the most abundant trace metal and is needed to make hemoglobin. Iron deficiency results in anemia and is most commonly seen in children with inadequate dietary intake; adults who exhibit chronic blood loss; and multiparous females who have not received iron supplementation. Iron excess is most often caused by increased ingestion and absorption of iron supplements or exposure from iron pots used for cookware. Some persons absorb excessive iron for unknown reasons. Accumulation of iron in the tissues leads to hemochromatosis which results in renal damage, cirrhosis, and an enlarged spleen and liver. The pancreas may become damaged leading to diabetes mellitus and deposition in other tissues causes inflammatory damage (e.g., deposits in joints cause arthritis).
• Lead (Pb): Lead is found in old paint, some ceramic products, lead-soldered water pipes, industrial waste, car exhaust, and cigarette smoke. Excessive amounts cause anemia, renal tubular nephrosis, diminished intellectual capacity and developmental delays in children, headache, drowsiness, and gastrointestinal upset.
• Manganese (Mn): Manganese is found in paint, cleaners for laboratory glass, and red brick. Excessive exposure to manganese dust in miners can cause pneumonitis. Chronic poisoning usually results from industrial exposure. Manganese accumulates in the brain causing symptoms similar to Parkinson's disease.
• Mercury (Hg): Mercury is used in the manufacture of paper, plastics, paint, and dental amalgams. The two most common sources of exposure are industrial pollution and ingestion of seafood containing methyl mercury, which is toxic. Excessive exposure can cause pulmonary, brain, kidney, liver, and gastrointestinal damage.
• Nickel (Ni): Nickel is used in industrial processes as a catalyst and as an alloy for steel and other metals. Skin contact causes eczema in sensitive individuals. Ingestion of toxic levels can result in headache, vomiting, vertigo, and nausea. Inhalation of toxic levels can cause asthma and a pneumonia-like condition.
• Selenium (Se): Selenium is a micronutrient needed for normal heart function, and deficiency leads to cardiomyopathy. Selenium deficiency is seen in regions where soil and water are depleted of minerals. It occurs in persons with gastrointestinal malabsorption, patients with kidney disease receiving dialysis, and patients receiving total parenteral nutrition. Excess toxicity is most commonly caused by excessive dietary supplementation and causes cirrhosis, enlarged spleen, hair loss, and gastrointestinal bleeding.
• Thallium (Tl): Thallium is used during the lead smelting process and as a rodent killer. Excessive amounts can cause hair loss, confusion, seizures, paralysis, and kidney failure.
• Zinc (Zn): Zinc is the second most abundant trace metal. Zinc deficiency is usually associated with total parenteral nutrition and drugs that prevent absorption, but a genetic deficiency causing reduced gastrointestinal absorption is also a rare cause. Deficiency causes dermatitis, diarrhea, impaired growth, hypogonadism, anemia, enlarged liver, hair loss, and decreased immune function. Zinc is used in metal plating and excessive exposure can cause fever; and skin, throat, and gastrointestinal irritation.

Lead poisoning

Children are often screened for lead poisoning since even very low levels of lead in their body can impact growth, learning, and intelligence. Before 1970, high levels of lead were routinely found in paints. A child has an increased risk of lead exposure if he or she lives in an older, dilapidated house that contains lead paint. As the paint chips and peels, young children, especially those six months to six years old, are at particular risk since they are young enough to put chips, dust, or their contaminated fingers in their mouths. The daily diet normally contains a small amount of lead, approximately 300 micrograms per day. Adults absorb 1-10% of ingested lead, but children absorb lead more efficiently putting them at greater risk for toxicity.

Suspected cases of lead poisoning can be pre-sumptively diagnosed with two surrogate tests. Lead blocks the incorporation of iron into protoporphyrin, resulting in the inability to form heme, the iron-containing component of hemoglobin. This results in increased levels of erythrocyte zinc protoporphyrin (ZPP) in which protoporphyrin is bound to zinc instead of iron and free erythrocyte protoporphyrin (FEP). Both ZPP and FEP can be measured by fluorometric analysis. However, both are also increased in iron deficiency, aluminum poisoning, and erythropoietic porphyria as well as lead poisoning.

Preparation

Usually, there is no special preparation for the patient before testing.

Aftercare

Since only a small sample of blood (or urine) is collected, no complex aftercare is required. The patient should be comforted (especially young children), and direct pressure should be applied to the venipuncture or finger stick site for several minutes or until the bleeding has stopped.

Complications

In normal circumstances, a blood draw for a heavy metal test takes only a few minutes, and the patient experiences minor discomfort and a minute puncture wound at the site of the needle stick.

Results

Reference ranges for specific metals are provided based on the type of testing performed by the laboratory, the specimen provided, and the type of metal tested. Representative ranges are shown below:

• Aluminum: less than 6 micrograms per liter.
• Arsenic: in urine less than 100 micrograms per liter (in whole blood less than 70 micrograms per liter).
• Cadmium: less than 5 micrograms per liter.
• Chromium: 0.5-2.1 micrograms per liter (urine 0.5-5.0 mcg/L).
• Copper: 75-150 micrograms per liter.
• Iron: 500-1500 micrograms per liter.
• Lead: Normal in children: less than 100 micrograms/L; Normal in adults: less than 300 micrograms/L.
• Lead (in ZPP testing for lead poisoning): Normal in children and adults: 15-77 micrograms/dL; Average: less than 35 micrograms/dL.
• Manganese: less than 7.9 micrograms per liter.
• Mercury: less than 5 micrograms per liter.
• Nickel: less than 5.2 micrograms per liter urine.
• Selenium: 95-160 micrograms per liter.
• Thallium: less than 10.1 micrograms per liter.
• Zinc: 50-150 micrograms per liter.

Health care team roles

A physician orders trace metal tests and interprets the results. The nurse, physician assistant, or nurse practitioner may participate in the medical examination of the patient, and should perform a careful history in order to document any environmental source of metal exposure (such as working in a battery manufacturing plant, automobile paint shop, etc.) that could be linked to the symptoms. A nurse or phlebotomist collects the specimen for trace metal tests. Trace metal analysis is performed by clinical laboratory scientists/medical technologists with special training in the use of atomic absorption spectrophotometry.

Additionally, health care providers should contact community health officials if the poisoning is acquired by an industrial or environmental exposure that may affect other people.

KEY TERMS

Edematous— The state of swelling (edema) caused by the collection of excess fluid within tissues.

Hematoma— Swelling and subsequent bruising when blood leaks from a vein into local tissues; can be caused by improper venipuncture when the needle has gone through a vein or when the needle has been inserted incorrectly.

Hemodialysis— Procedure used to filter toxins and waste products from the blood while the blood circulates outside the body; dialysis is used for patients with kidney failure.

Venipuncture— Puncture of a vein with a needle for the purpose of withdrawing a blood sample for analysis.

Patient education

The health care provider's role in educating patients about trace metal poisoning is crucial, especially in cases of suspected lead poisoning in children. The health care provider should explain how lead poisoning is acquired, and work with the parents to determine the lead source. Since the health complications for children are serious, it is vital that the parents understand that treatment may be needed immediately and further testing will be required to monitor the lead level and its effects. The health care provider can work with adult patients to determine the source of metal in their homes or work environments and inform them about treatment and follow-up testing requirements.

Resources

BOOKS

Fischbach, Frances. "Lead." In A Manual of Laboratory & Diagnostic Tests. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2000, pp.398-400.

Kee, Joyce LeFever. "Lead (Blood)" and "Zinc Protoporphyrin (ZPP) (Blood)." In Laboratory & Diagnostic Tests with Nursing Implications. 5th ed. Stamford, CT: Appleton & Lange, 1999, pp.281-282, 460-461.

Mofenson, Howard C., et al. "Acute Poisonings: Lead." In Conn's Current Therapy 2001. edited by Robert E. Rakel and Edward T. Bope. Philadelphia: W.B. Saunders Company, 2001, pp.1230-1235.

Moyer, Thomas P. "Toxic Metals." In Tietz Textbook of Clinical Chemistry. 3rd ed., edited by Carl A. Burtis and Edward R. Ashwood. Philadelphia: W. B. Saunders Company, 1999, pp.982-998.

Sacher, Ronald A., Richard A. McPherson, with Joseph M. Campos. "Heavy Metals." In Widmann's Clinical Interpretation of Laboratory Tests. 11th ed. Philadelphia: F. A. Davis Company, 2000, pp.919-921.

ORGANIZATIONS

Alliance to End Childhood Lead Poisoning. 227 Massachusetts Ave., N.E., Suite 200, Washington, D.C. (202) 543-1147. 〈http://www.aeclp.org〉.

Lead Poisoning Prevention Branch, Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention. 1600 Clifton Rd., Mailstop E25, Atlanta, GA. (404) 498-1420. 〈http://www.cdc.gov/nceh/lead〉.